Several mutations have been introduced into a cloned human TGF-alpha gene by site-directed mutagenesis. These mutants will be expressed to study structure-activity relationships of TGF-alpha. The rat TGF-alpha gene has been chemically synthesized for further in vivo studies in rats. The rat TGF-alpha gene will be inserted into a vaccinia virus vector and then used to immunize rats against TGF-alpha activity. An anti-sense rat TGF-alpha gene has been constructed using a retrovirus vector and will be used in an attempt to inhibit specific expression of TGF-alpha.